Wednesday, January 31, 2007

If you knew that you were especially susceptible to heart disease when you gained weight, would it increase your motivation to diet? How much would you be willing to pay to find out if you are one of the lucky people who can eat as much fat as you want and not have an increased risk of heart disease? Such tests are the goal of nutrigenomics, which seeks to identify the links between nutrition and disease based on an individual's genome.

While the field is still too young to offer personal dietary advice for the average consumer, research has uncovered links among genes, diet, and heart disease. Jose Ordovas, director of the Nutrition and Genomics Laboratory at Tufts University, has spent years studying the link between metabolism of dietary fats and risk of cardiovascular disease. After analyzing data from the Framingham Heart Study, a large-scale study that has traced the health of some 5,000 people since 1948, his team has found that certain genetic variants can protect people from diet-induced cardiovascular disease--or put them at increased risk. Ordovas spoke with Technology Review about his research and the future of the field.

A good article about A microfluidic chip that rapidly identifies pathogens by scanning their genomes.

From the article :

When a patient is admitted to the hospital with signs of a dangerous systemic bacterial infection, or when a post-office worker finds white powder in a suspicious-looking envelope, the ability to quickly identify potential pathogens is important. To accomplish that, a team of Massachusetts researchers is developing a microfluidic chip that performs fast DNA sequencing to rapidly identify bacteria. The goal is a device simple enough to use in airport and other security screening.

In order to identify the bacteria in a blood sample or in a building's ventilation system, researchers or clinicians usually must start by coaxing it to grow in culture in the lab. This takes about 14 to 48 hours. In the meantime, a patient with a drug-resistant infection may be given the wrong antibiotic, or emergency medical workers may miss the signs of a potential bioterror attack.

Monday, January 29, 2007

The gene-activating method, which is being developed by UT Southwestern scientists, also is providing researchers with a novel research tool to investigate the role that genes play in human health.

In a paper appearing online at Nature Chemical Biology and in an upcoming edition of the journal, lead author Dr. Bethany Janowski, assistant professor of pharmacology at UT Southwestern, and her colleagues describe how they activated certain genes in cultured cells using strands of RNA to perturb the delicately balanced mixture of proteins that surround chromosomal DNA, proteins that control whether genes are turned on or off.

Dr. David Corey, professor of pharmacology and the paper's senior author, said the results are significant because they demonstrate the most effective and consistent method to date for coaxing genes into making the proteins that carry out all of life's functions - a process formally called gene expression.

In any medical specialty, Dr. Janowski said, there are conditions where increased gene expression would prove beneficial.

"In some disease states, it's not that gene expression is completely turned off, but rather, the levels of expression are lower than they should be," she said. As a result, there is an inadequate amount of a particular protein in the body. "If we can bring the level up a few notches, we might actually treat or cure the disease," Dr. Janowski said.

For example, some genes are natural tumor suppressors, and using this method to selectively activate those genes might help the body fend off cancer, Dr. Janowski said.

Genes are segments of DNA housed in chromosomes in the nucleus of every cell and they carry instructions for making proteins. Faulty or mutated genes lead to malfunctioning, missing or over-abundant proteins, and any of those conditions can result in disease.

Surrounding the chromosome is a cloud of proteins that helps determine whether or not a particular gene's instructions are "read" and "copied" to strands of messenger RNA, which then ferry the plans to protein-making "factories" in the cell.

In its experiments, the UT Southwestern team used strands of RNA that were tailor-made to complement the DNA sequence of a specific gene in isolated breast cancer cells. Once the RNA was introduced into the protein mix, the gene was activated, ultimately resulting in a reduced rate of growth in the cancer cells.

Dr. Corey said that while it's clear the activating effects of the new technique are occurring at the chromosome level, and not at the messenger RNA level, more research is needed to understand the exact mechanism.

Although the RNA strands the researchers introduced - dubbed antigene RNA - were manufactured, Dr. Corey said the process by which they interact with the chromosome appears to mimic what naturally happens in the body.

"One of the reasons why these synthetic strands work so well is that we're just adapting a natural mechanism to help deliver a man-made molecule," Dr. Corey said. "We're working with nature, rather than against it."

Drs. Corey's and Janowski's current results are built on previous work, published in 2005 in Nature Chemical Biology, in which they found that RNA strands could turn off gene expression at the chromosome level.

The new UT Southwestern research, coupled with that from 2005, demonstrates a shift away from conventional thinking about how gene expression is naturally controlled, as well as how scientists might be able to exploit the process to develop new drug targets, Dr. Corey said.

For example, current methods to block gene expression, such as RNA interference, rely on using RNA strands to intercept and bind with messenger RNA. While RNA interference is an effective tool for studying gene expression, Dr. Janowski said, it's more efficient to use RNA to control both activation and de-activation at the level of the chromosome.

"It goes right to the source, right to the faucet to turn the genes on or off," she said.

Dr. Corey said many researchers have the ingrained idea that RNA only targets other RNA - such as what occurs when messenger RNA is targeted during RNA interference. "That's what everyone is familiar with," he said. "But the idea of RNA being used as a sort of nucleic acid modulator of chromosomes, at the level of the chromosome itself, is novel and unexpected, and it's going to take some getting used to."

A tiny startup says it has created a stretch of DNA more than 35,000 letters long.

The company, Codon Devices of Cambridge, Mass., believes it is the longest piece of DNA ever ever commercially shipped--but that's only the latest step in a race to create bigger and bigger pieces of genetic material.

Codon is aiming to become the leading player in a new field called "synthetic biology," creating tools by which cells and their genetic material can be more precisely engineered in order to create new medicines and industry. In this case, the DNA was constructed for Microbia, another Cambridge biotech that is developing drugs and creating microbes that can be used in manufacturing chemicals.

The creation of ever-longer stretches of man-made DNA is allowing researchers to make new strides in understanding how multiple genes work together.

"This is basically the next step in synthetic biology," says Brian Baynes, Codon's chief scientific officer. "People have been doing a lot of work with synthetic genes for a number of years, but they've been stuck with one gene."

On a piece of DNA as long as the one made for Microbia, ten or more genes may be present. By studying more than one gene at once, researchers hope to get a better picture of how they work in concert to produce an organism. Another advantage: These stretches can also be made to contain all the DNA letters that occur between genes. Scientists once thought of that stuff as junk, but many now believe it may regulate how the genes work or provide some other function.

Scientists playing in the synthetic-biology toolbox have also managed to make living cells do things nature never designed. One setup created blinking lights; another made photographic film composed of living bacteria in a Petri dish.

Codon was founded a year ago on the idea that scientists would need a company that could sell tools used in creating such custom-designed biological systems (see: " Photoshop For DNA").

Other companies are also in the business of making DNA for drug companies and other research organizations, which save time by using newer DNA synthesis methods instead of laboriously copying cells and inserting or deleting bits of genetic material.

Blue Heron Biotechnology, a company that is in the sole business of synthesizing DNA, says it made a piece of DNA that was 27,000 letters long while working with academic researchers. But the company says it sees itself as more of a supplier to synthetic biologists than as a player in the field. "I am optimistic that in a few years things like synthetic biology will be half or more of our market," says Chief Executive John Mulligan. "We're a pure DNA foundry."

Codon says that within a year or two it hopes to create DNA fragments that are as much as 100,000 letters long, and that eventually they might make 1-million-letter fragments.

"Codon's charge from the beginning has been to industrialize this space and create something well beyond synthetic biology that we call constructive biology," says Chief Executive John Danner. He says that by December of this year he hopes to have more DNA production capacity than all his competitors currently have combined.

Awesome stuff considering its just a start up...while we look out even more, stay tuned because, this blog is soon gonna be the definative Gene Synthesis Blog

CARLSBAD, Calif.--(BUSINESS WIRE)--Dec. 12, 2006--Invitrogen Corporation (Nasdaq:IVGN), a global leader in life sciences, today announced they have entered into a strategic development and distribution relationship with Blue Heron Biotechnology. Invitrogen will invest in Blue Heron in exchange for worldwide rights to distribute Blue Heron's custom gene synthesis services. Under the terms of the agreement, Invitrogen will become the exclusive worldwide distributor of Blue Heron's synthetic genes. The financial terms of the agreement were not disclosed.

Blue Heron Biotechnology's proprietary GeneMaker(R) platform can synthesize any gene sequence, with perfect accuracy regardless of length or complexity, which makes it ideal for the synthetic biology market. Researchers worldwide are increasingly turning to synthetic genes as a convenient, cost-effective alternative for traditional cloning. Accurate and rapid synthesis of synthetic genes has allowed pharmaceutical and biotechnology companies to speed the drug discovery process through an ability to rapidly and accurately synthesize known genes, and produce from them novel proteins, new vaccines and diagnostics.

"Invitrogen recognizes the tremendous new possibilities that gene synthesis offers life science researchers," said Nathan Wood, Vice President of Cloning and Protein Expression. "We have developed a broad array of products that complement Blue Heron's GeneMaker(R) platform and this agreement continues to enhance our portfolio offerings to our customers."

Invitrogen is a leading provider of recombinant cloning and protein expression products, as well as the premier provider of the largest fully sequenced human open reading frame clone collections. Gene synthesis builds upon this strength and will be especially useful in emerging fields such as synthetic biology.

"Partnering with a life sciences leader such as Invitrogen is an important milestone in Blue Heron Bio's continued growth and signals an important milestone for the overall gene synthesis market as well. We are very pleased to be able to make our gene synthesis services available through Invitrogen's unmatched distribution and marketing channels," said John Fess, CEO of Blue Heron Biotechnology.

As part of the agreement, the companies will co-develop new products and services for the research and bio-pharmaceutical markets.

Many cancers arise due to defects in genes that normally suppress tumor growth. Now, for the first time, MIT researchers have shown that re-activating one of those genes in mice can cause tumors to shrink or disappear.

The study offers evidence that the tumor suppressor gene p53 is a promising target for human cancer drugs.

"If we can find drugs that restore p53 function in human tumors in which this pathway is blocked, they may be effective cancer treatments," said David Kirsch of MIT's Center for Cancer Research and Harvard Medical School, one of the lead co-authors of the paper.

The study is published in the Jan. 24 online edition of Nature. It was conducted in the laboratory of Tyler Jacks, director of the Center for Cancer Research, the David H. Koch Professor of Biology and a Howard Hughes Medical Institute investigator.

P53 has long been known to play a critical role in the development of many tumors--it is mutated in more than 50 percent of human cancers. Researchers have identified a few compounds that restore p53 function, but until now, it has not been known whether such activity would actually reverse tumor growth in primary tumors.

The new MIT study shows that re-activating p53 in mouse tumors dramatically reduces the size of the tumors, in some cases by 100 percent.

"This study provides critical genetic evidence that continuous repression of a tumor suppressor gene is required for a tumor to survive," said Andrea Ventura, an Italian postdoctoral associate in the Center for Cancer Research and first author of the paper.

In normal cells, p53 controls the cell cycle. In other words, when functioning properly, it activates DNA repair mechanisms and prevents cells with damaged DNA from dividing. If DNA damage is irreparable, p53 induces the cell to destroy itself by undergoing apoptosis, or programmed cell death.

When p53 is turned off by mutation or deletion, cells are much more likely to become cancerous, because they will divide uncontrollably even when DNA is damaged.

In this study, the researchers used engineered mice that had the gene for p53 turned off. But, they also included a genetic "switch" that allowed the researchers to turn p53 back on after tumors developed.

Once the switch was activated, p53 appeared in the tumor cells and the majority of the tumors shrank between 40 and 100 percent.

The researchers looked at two different types of cancer--lymphomas and sarcomas. In lymphomas, or cancers of the white blood cells, the cancer cells underwent apoptosis within 1 or 2 days of the p53 reactivation.

In contrast, sarcomas (which affect connective tissues) did not undergo apoptosis but went into a state of senescence, or no growth. Those tumors took longer to shrink but the senescent tumor cells were eventually cleared away.

The researchers are not sure why these two cancers are affected in different ways, but they have started trying to figure it out by identifying the other genes that are activated in each type of tumor when p53 turns back on.

The study also revealed that turning on p53 has no damaging effects in normal cells. The researchers had worried that p53 would kill normal cells because it had never been expressed in those cells.

"This means you can design drugs that restore p53 and you don't have to worry too much about toxic side effects," said Ventura.

Possible therapeutic approaches to turn on p53 in human cancer cells include small molecules that restore mutated p53 proteins to a functional state, as well as gene therapy techniques that introduce a new copy of the p53 gene into tumor cells. One class of potential drugs now under investigation, known as nutlins, acts by interfering with MDM2, an enzyme that keeps p53 levels low.

In follow-up studies, the MIT researchers are looking at other types of cancer, such as epithelial (skin) cancer, in their mouse model, and they plan to see if the same approach will also work for tumor suppressors other than p53.

This research was funded by the Howard Hughes Medical Institute, the National Cancer Institute, the American Italian Cancer Research Foundation and the Leaf Fund.

Other authors on the paper are Margaret McLaughlin, a former postdoc in Jacks' lab, now at Novartis; David Tuveson, also a former postdoc, now group leader at the Cambridge Research Institute (United Kingdom); Laura Lintault, a research affiliate in the Center for Cancer Research; Jamie Newman, graduate student in MIT's Department of Biology; Elizabeth Reczek, a former graduate student in Jacks' lab, now a postdoctoral fellow at Brigham and Women's Hospital; Ralph Weissleder, a professor of radiology at Harvard Medical School and director of the Center for Molecular Imaging Research; and Jan Grimm, a former postdoc in Weissleder's lab, now at Memorial Sloan Kettering Cancer Center.

Every human being has 20,000 to 25,000 genes that determine the growth, development and functions of our physical and biochemical systems. Genes are normally packaged into 46 chromosomes (23 pairs) inside our cells.

The pairs numbered 1 to 22 are the same in males and females and are called autosomes. The 23rd pair are sex-determining chromosomes. Females have two Xs and males have one X and one Y.

Sperm and egg cells are different from other body cells. These reproductive cells each have only 23 unpaired chromosomes. When a single sperm and egg come together when pregnancy begins they form their own new cell with 46 chromosomes. The human being that results is genetically unique, with a blueprint half from each parent.

just to round up on that a bit, i was eagerly looking at some ads that would show companies lookin at this technology.. for one we know that, world wide, Codon Devices gives 1bp at $0.79 !! that is like really low and based on what I've read about Codon Devices, they're pretty good.. also now we have a new contender for their title.. GenScript now is in with $0.75 per base pair!! Hey i'm not tryin to promote any brand here and I don't certainly make the news.. i just see em..

I know this is old stuff, but as usual the definative Gene Synthesis Blog brings u news that could impact the industry... read on...

SAN DIEGO—Illumina Inc. and Solexa Inc. announced in mid-November a definitive agree­ment under which Illumina will acquire Solexa in a stock-for-stock merger. Under the merger agreement, Solexa stockholders would receive Illumina common stock valued at $14 per share, for a total equity value of approxi­mately $600 million. Illumina also agreed to invest $50 million in Solexa in exchange for newly issued Solexa shares.

The merger announcement comes just months after Solexa began moving its next-generation sequencing platform, the 1G Genome Analyzer, to a handful of select customers and prepares to aggressively launch the product to the broader market in 2007. Furthermore, it joins together compa­nies that have plied the waters of both gene expression and gene sequencing, mar­kets that Illumina officials say are highly complementary and that it estimates in excess of $2.25 billion.

“For around the last 18 months, we and our CEO [Jay Flatley] have been looking at next-generation sequencing technolo­gies,” says John Stuelpnagel, COO of Illumina. “We knew that what we are doing in genotyping and gene expression had great overlap and synergies and that the tech­nologies could play off each other.”

Specifically, Illumina sees cross selling and integration opportuni­ties for researchers using Solexa’s 1G Genome Analyzer for whole-genome resequencing to use those results to conduct additional work on Illumina’s BeadStation for whole-genome genotyping. Likewise, results from the BeadStation for targeted genotyping studies could suggest additional work for target­ed resequencing appropriate for the 1G Genome Analyzer.

“This merger will create the only company today that can offer both analog and digital gene expression,” notes Stuelpnagel. “From Illumina’s standpoint, it was also an opportunity to bring in a sequencing technology that is much farther along than com­peting technologies and to rapidly commercialize it.”

For Solexa, the time to join with Illumina was suitable as it pre­pares to ramp up the production and marketing of its 1G product—a system it maintains has the poten­tial to generate “upwards to 1 bil­lion bases of data in a single run.” The company also says it can cur­rently sequence an entire genome for around $100,000, a figure that is orders of magnitude separated from its nearest competitor.

“We started talking with Illumina about a collaboration to help us with our sequencing tool,” says Omead Ostadan, VP of mar­keting for Solexa. “But as we con­tinued to talk, what we found was there was much more we could do as a company by merging with them both from a technology and a technical standpoint.”

While Solexa will benefit from Illumina’s large sales and support footprint in the global market, there are also opportunities for Illumina’s manufacturing infra­structure to help with the com­mercial ramp up of the 1G.

Still, Stuelpnagel notes, there is no intention of significantly chang­ing the operations at Solexa’s two operating centers in Hayward, Calif. and Cambridge, England.

When the merger is completed, expected in the first quarter of 2007, current Solexa CEO John West will stay on with the compa­ny as senior VP and general man­ger of the sequencing business.

Tuesday, January 23, 2007

British scientists have taken animportant step toward preventing tumor growth by finding a way ofswitching off a gene involved in cell division.

The Oxford University researchers say the mechanism involves a formof ribonucleic acid, or RNA, a chemical found in cell nuclei. RNA playsa direct role in the synthesis of proteins, but scientists have knownfor some time that not all types of RNA are directly involved inprotein synthesis.

Now, in research funded by the Wellcome Trust and Britain's MedicalResearch Council, the Oxford scientists have shown one particular typeof RNA plays a key role in regulating the gene implicated in control oftumor growth.

"There's been a quiet revolution taking place in biology during thepast few years over the role of RNA," said Alexandre Akoulitchev, asenior research fellow at the university. "Scientists have begun to see'junk' DNA as having a very important function. The variety of RNAtypes produced from this "junk" is staggering and the functionalimplications are huge."

BRISBANE, Calif., Jan. 22 /PRNewswire/ -- For many Americans livingwith a heart transplant, invasive heart-muscle biopsies that check fororgan rejection are a fact of life. However, a simple blood test thatanalyzes a patient's genes, introduced in 2005, has been evaluated byleading transplant centers and their experience verifies it canaccurately detect the absence of heart transplant rejection, accordingto data reported in a new study authored by a consensus team ofinternational heart transplant experts and published in the December2006 edition of the Journal of Heart and Lung Transplantation (JHLT).

In 2006, results from the CARGO (Cardiac Allograft Rejection GeneExpression Observational) study were published and reported on theutility of a gene expression profiling (GEP) test, called AlloMap(R)molecular expression testing, which had been commercially available fornearly a year. Developed by XDx, a molecular diagnostics company inBrisbane, Calif., the test is currently offered at 40 transplantcenters in the United States.

"AlloMap testing is not only lessinvasive and less risky than biopsy, it also monitors the absence oforgan rejection and raises the suspicion of damage before any damage tothe heart happens. Biopsy records damage that has already occurred,"says Dr. Mario Deng, the article's corresponding author. Dr. Deng isdirector of cardiac transplantation research and associate professor ofclinical medicine at Columbia University College of Physicians andSurgeons, and a practicing cardiologist at NewYork-Presbyterian/Columbia University Medical Center.

Approximately 30 percent of all heart transplant patients reject theirnew heart at least once in the first year after transplantation. Whentesting reveals organ rejection, a patient's immunosuppressive regimenis adjusted.

"The Cleveland Clinic was the first transplantcenter in the United States to use the AlloMap test to follow patientsafter cardiac transplant," said Dr. Randall C. Starling, theeditorial's first author and vice chairman of cardiovascular medicineand section head of heart failure and cardiac transplant medicine atCleveland Clinic. "There is clearly a need for new methods to determinethe best way to manage heart transplant patients. Gene expressionprofiling appears to be the future, and holds the potential to improveaccuracy of diagnosis, reduce the need for invasive procedures andreduce cost. Additional research is necessary, but we are encouragedthat gene expression profiling will improve the care of our patients."

Based on the new data published as an invited editorial, in morethan 99 percent of cases, the AlloMap test successfully predicted theabsence of moderate or severe acute cellular organ-transplantrejection. These results confirm the findings of the CARGO study.

The AlloMap test was developed to rule out rejection, meaning that alow test score very reliably identifies transplant patients who are notrejecting their transplanted heart. The primary advantage of the testis to identify low-risk patients who can be monitored and managed usingnoninvasive methods and who may benefit from being more aggressivelyweaned off intensive immunosuppressive regimens that are associatedwith serious side effects.

"Many of the premier transplantcenters in the United States have incorporated AlloMap testing intotheir treatment protocol and physicians are relying on the test toaccurately manage the care of heart transplant recipients," said PierreCassigneul, president and chief executive officer of XDx. "The invitededitorial in JHLT further validates the usefulness and accuracy ofAlloMap testing. We are pleased to see continued confirmation of thetest's abilities from real-world use."

The AlloMap test wasdeveloped by XDx in partnership with eight major U.S. researchuniversities and presents current immune activity of the transplantedheart recipient. The test uses real-time polymerase chain reaction(PCR) and an algorithm to analyze the patient's gene expression. TheAlloMap test is currently being developed for use in lungtransplantation.

Before the availability of AlloMap testing,heart-muscle biopsy was the only method available for detectingrejection of the transplanted heart. Invasive heart biopsies areperformed frequently in the first year post-transplant and periodicallythereafter, often for the patient's lifetime.

Currently, the AlloMap test is available to heart transplant patients, ages 15 and older, two months post-transplantation.

The value of the primaryand secondary U.S. biomanufacturing market in 2006 is estimated to beapproximately $50 billion with a healthy growth rate almost approachingdouble digits due to the escalating number of biotech drugs in thepipeline and skyrocketing sales of approved high-value, life-savingbiopharmaceuticals.

The current economic and regulatoryreality, highlighted by the imminent establishment of drug pricingcontrols and tightening regulatory and quality standards, indicates theadded pressures that are emerging for pharmaceutical companies tore-strategize their overall approach. There is a trend toward fewerblockbuster drugs, as patient populations become smaller and theassociated histories and genetic makeup become stratified aspersonalized medicine begins to come into its own.

Biodisposablemanufacturers have responded to these trends by developing fullyintegrated, turnkey manufacturing–production lines that combinesingle-use components with modular software, disposable bioreactors andequipment, and a disposable stir-tank and mixing system.

Marketresearch necessary to design and implement a disposable biotechfacility is summarized in this report, including the latest disposabletechnologies and applications from leading industry users. In addition,detailed examples for analyzing cost of goods and savings are providedto assist professionals attempting to determine the utility ofdisposables in their own facility.

The biopharmaceuticalindustry in the U.S. grew by an average of 11% annually from 1993 to2003. Cartridges used for filtering liquids represent a $10.8 billiondollar market now, but by 2009, sales will reach an annual level of$14.2 billion. The market for membrane technology used inbiopharmaceutical discovery, development, and commercial production,estimated at $740 million in 2004, is expected to rise at an averageannual growth rate of 10.7% to more than $900 million in 2008 and to$1.23 billion in 2009. The average time required to construct a biotechfacility is about five years, putting tremendous pressure on drugmanufacturers to expend capital when the risk of drug failure is stillhigh. Existing manufacturing plant costs linger between $10–50 million,depending upon required output and therapeutic bioproduct. At the twoextreme price ranges, a 100-L, $10,000 Mab plant scales up to a10,000-L plant costing $120 million.

Within the next fiveyears, it is expected that 25% of all drugs will be biologicalproducts. As discovery and production of these products relies heavilyon membranes, hundreds of membrane products (many single-use) andprocesses will continue to be developed to meet the emerging market.

JefferyTerryberry has over a dozen peer-reviewed publications in clinicalchemistry research focusing on orthobiologic drug development. GautamThor is the author of scientific and medical publications throughNeuroConsultants. For sample content from D/&/amp;MD’s “Biodisposables:Utility and Technological Advances” report: www.drugandmarket.com/9215.E-mail: cust.serv@drugandmarket.com.

The last few years have been very good to ribonucleic acid (RNA).Decades after DNA took biology by storm, RNA was considered little morethan a link in a chain--no doubt a necessary link, but one that, byitself, had little to offer. But with the discoveries of RNAinterference and microRNAs, this meager molecule has been catapulted tostardom as a major player in genomic activity.

Now, a team ofscientists led by David Bartel, a professor in MIT's Department ofBiology, has discovered an entirely new class of RNA molecules.

Reportingin the journal Cell, the team describes identifying more than 5,000 ofthese new molecules, termed 21U-RNAs, in the C. elegans worm. These newRNAs are named after their distinctive features: Each molecule contains21 chemical building blocks (or nucleotides), and each begins with thechemical uridine, represented by the letter U (the only RNA nucleotidenot also found on DNA). In addition, each of the 5,000 different21U-RNA molecules comes from one of two chromosomal regions.

Further,"we can predict where additional 21U-RNA genes might reside," saysBartel, who is also a member of the Whitehead Institute for BiomedicalResearch and a Howard Hughes Medical Institute investigator. "Combiningthese predictions with the 5,000 (21U-RNAs) that we experimentallyidentified, we suspect that there are more than 12,000 different21U-RNA genes in the genome." Because each gene typically produces aunique 21U-RNA, a very large diversity of molecules is made.

"Thereare so many 21U-RNA genes spread out over such a wide swath of thegenome, but they all share common requirements for expression andcommon structural features," says Bartel lab Ph.D. student J. GrahamRuby, lead author on the paper.

Although the researchers haven'tyet identified a particular function for these molecules, they believethat this uniform structure strongly indicates an important role.

MITInstitute Professor and Nobel Laureate Phillip Sharp, a biologist whowas not part of the research team, supports this hypothesis. The factthat 21U-RNAs share this "common structure and origin suggests animportant function," he says. "It requires function to conservespecificity."

Other members of the research team are affiliatedwith the Broad Institute of MIT and Harvard and Pennsylvania StateUniversity. This research was supported by the Prix Louis D from theInstitut de France and a grant from the National Institutes of Health.

Parkinson’s disease (PD) is a progressive neurodegenerative disorderthat is difficult to diagnose until significant cell loss has alreadyoccurred in the substantia nigra, as evidenced by abnormally slowmovement and tremor. Even then, other neurological diseases mayconfound a clinical diagnosis.

Theauthors of this study provide a first-pass at identifying a set ofgenetic markers for diagnosing PD. Their work entailed screening venousblood of 31 PD patients and 35 controls, 18 of whom had otherneurological diseases such as Alzheimer’s disease and progressivesupranuclear palsy. The microarray analysis used more than 22,000oligonucleotide probes to find differences in RNA content of the blood.Eight unrelated genes that are expressed in the brain were identified,including three implicated in PD: the vitamin D receptor, huntingtininteracting protein 2, and a protein involved in dopamine transporterendocytosis. The other five have not been associated with PDpreviously.

A test of the biomarker’s accuracy found that therewas a significant difference between patients with PD and the normaland disease controls. Those with a score in the highest third had anodds ratio of 5.1 for PD, versus 1.9 for the intermediate third ofpatients. (The lowest third was used as a reference group with anassigned score of 1.)

The microarray analysis also identified22 genes whose expression was altered in PD patients, but lackedpredictive power since they were found at abnormal levels in otherneurodegenerative diseases. Further investigation of these genes seemswarranted, as they may shed light on disease pathology. Indeed, one,the heat-shock protein 70-interacting protein ST13 gene may afford anopportunity to follow disease progression.

In all, this studyprovides enticing leads to follow for the development of abiomarker-based diagnostic test for Parkinson’s disease, as well as anassay for assessing disease progression.

A new method for synthesizing specific DNA sequences could revolutionize the production of genes in the laboratory (Nature, 23 Dec 04, Vol. 432, No. 7020, pp. 1050-1054). The technique, which uses programmable 'DNA microchips', looks set to slash the current cost of gene synthesis.

The DNA microchips are tagged with thousands of different short DNA sequences called oligonucleotides. These form two groups: 'construction' oligonucleotides, which act as templates for the replication of corresponding genetic sequences, and 'selection' oligonucleotides, which reinforce production of the correct sequences to minimize errors. A single-step reaction then assembles these short DNAs into much longer stretches of sequence.

To test their method, George Church and his colleagues assembled all 21 genes used by the bacterium Escherichia coli to create one part of its protein-assembly apparatus, called the ribosome. By tweaking the sequences of the construction oligonucleotides, they were able to increase the efficiency with which these genes were translated into protein, bringing closer the goal of creating a complete artificial ribosome in the lab. If successful, the technique could radically cut the cost of assembling gene sequences, which currently yields about nine DNA 'letters' for every dollar spent. The researchers hope that with this new method, a dollar could potentially buy 20,000 letters of highly accurate code.

Columbia University announces today that it recently executed anexclusive license agreement for a next generation DNA sequencingtechnology to Intelligent Bio-Systems (IBS), Inc. This innovativeDNA-sequencing technology was invented by Dr. Jingyue Ju, professor ofChemical Engineering and head of DNA Sequencing and Chemical Biology atthe Judith P. Sulzberger, M.D. Columbia Genome Center at ColumbiaUniversity. The fundamentals of this new technology are being publishedon-line today by in the Proceedings of the National Academy of Sciences(PNAS). This research paper describes the details of the Sequencing bySynthesis Chemistry and how the approach overcomes accuracy limitationsof other next generation DNA sequencing systems.

It was also recently announced that Columbia University incollaboration with the Waltham, Mass. based Intelligent Bio-Systems, isone of only two recipients of the Near-Term Technology Development forGenome Sequencing grants from the National Human Genome ResearchInstitute (NHGRI) of the National Institutes of Health (NIH)(www.genome.gov/19518500). This grant of $425,000 is for thedevelopment of a "High-Throughput DNA Sequencing by Synthesis Platform."

"The collaboration between Dr. Ju at Columbia and IntelligentBio-Systems is an important development to bring this powerfultechnology to both researchers and clinicians in the near future," saidDr. Steven Gordon, Chief Executive Officer at IBS. "Completing thelicense was a key step in uniting Dr. Ju's seminal sequencing chemistryand IBS's molecular biology and engineering expertise. We are poised tooffer a simple, cost effective platform that will enable manyresearchers and clinicians to use this next-generation DNA sequencingtechnology in their own laboratories."

Dr. Ju is a prolific inventor of new technologies forapplications in genomics using chemistry and molecular engineeringapproaches. He is credited with being one of the primary inventors ofthe fluorescent energy transfer chemistry for 4-color Sanger sequencingbeing used by virtually all of the current generations of DNAsequencers that were used to complete the Human Genome Project.

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About Columbia Genome Center

From its conception in 1995, the Judith P. Sulzberger, M.D.,Columbia Genome Center (CGC) has served as a bridge between thebiomedical and science/engineering communities of the two ColumbiaUniversity campuses, the main campus in Morningside Heights and theMedical Center campus in Washington Heights. The CGC was born as aninterdisciplinary consortium of scientists and engineers dedicated tothe generation of technology, information science, systems biology, andpopulation genetic theory required to transform information from thegenome to the study of biology and the practice of medicine. Today,more than 70 scientists collaborate on initiatives to furtherilluminate the genome.

About Columbia University

Founded in 1754 as King's College, Columbia University in theCity of New York is the fifth oldest institution of higher learning inthe United States and is one of the world's leading academic andresearch institutions, conducting pathbreaking research in medicine,science, engineering, the arts, and the humanities. For moreinformation about Columbia University, visit www.columbia.edu.

About Intelligent Bio-Systems, Inc.

Intelligent Bio-Systems, Inc. is a privately held companylocated in Waltham, Mass. Since founding in 2005 it has focused on thedevelopment of next-generation DNA sequencing, gene expression anddiagnostic systems based on proprietary instruments, chemistry, andconsumables. The company has committed to deliver working instrumentsto the laboratories of a few early access collaborators during thecoming year.